ArticleJournal of medical virology2023
Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.
Article in Journal of medical virology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 19 citations in OpenAlex.
- DDX17 and viral infection.Virulence · 2026Review
- Structure-guided discovery and engineering of miniature CRISPR-Cas12m for epigenome editing.Nature structural & molecular biology · 2026Article
- AAV-mediated delivery of CRISPR/Cas9 targeting conserved overlapping ORFs efficiently suppresses HBV replication in hepatocyte models.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Combined RNA- and DNA-targeting CRISPR ribonucleoproteins enhance suppression of HBV transcripts.Frontiers in genome editing · 2026Article
- Extracellular Vesicles for Therapeutic Applications: A Translational Framework Integrating Sources, Administration Routes, Indications, Quality Control, and Regulatory Systems.International journal of nanomedicine · 2026Review
- Article
- Suppression of HBV replication and expression by CRISPR/Cas9 ribonucleoproteins.Antiviral research · 2026Article
- Disrupting Viral Persistence: CRISPR/Cas9-Based Strategies for Hepatitis B and C Treatment, and Challenges.Journal of cellular and molecular medicine · 2026Review
- Highly stable Cas9 promotes HBV genome destruction by antagonizing HSC70-mediated degradation.Emerging microbes & infections · 2025Article
- Anticodon Engineered Transfer RNA (tRNAAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Engineering a High-Fidelity MAD7 Variant with Enhanced Specificity for Precision Genome Editing via CcdB-Based Bacterial Screening.Biomolecules · 2025Article
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Current status and challenges of therapeutic targets, novel drugs and delivery systems for hepatitis B: how far to our goal?Frontiers in cellular and infection microbiology · 2025Review
- Engineered exosomes: a promising drug delivery platform with therapeutic potential.Frontiers in molecular biosciences · 2025Review
- Therapeutic potential of exosomes in periodontal regeneration: Immunomodulatory and tissue-repair mechanisms.Frontiers in immunology · 2025Review
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.Journal of virology · 2024Article
- Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.Viruses · 2024Review
- The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.Biomarker research · 2024Review
- The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption.Frontiers in genome editing · 2024Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
The presence of hepatitis B virus (HBV) covalently closed circular (ccc) DNA (cccDNA), which serves as a template for viral replication and integration of HBV DNA into the host cell genome, sustains liver pathogenesis and constitutes an intractable barrier to the eradication of chronic HBV infection. The current antiviral therapy for HBV infection, using nucleos(t)ide analogues (NAs), can suppress HBV replication but cannot eliminate integrated HBV DNA and episomal cccDNA. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is a powerful genetic tool that can edit integrated HBV DNA and minichromosomal cccDNA for gene therapy, but its expression and delivery require a viral vector, which poses safety concerns for therapeutic applications in humans. In the present study, we used synthetic guide RNA (gRNA)/Cas9-ribonucleoprotein (RNP) as a nonviral formulation to develop a novel CRISPR/Cas9-mediated gene therapy for eradicating HBV infection. We designed a series of gRNAs targeting multiple specific HBV genes and tested their antiviral efficacy and cytotoxicity in different HBV cellular models. Transfection of stably HBV-infected human hepatoma cell line HepG2.2.15 with HBV-specific gRNA/Cas9 RNPs resulted in a substantial reduction in HBV transcripts. Specifically, gRNA5 and/or gRNA9 RNPs significantly reduced HBV cccDNA, total HBV DNA, pregenomic RNA, and HBV antigen (HBsAg, HBeAg) levels. T7 endonuclease 1 (T7E1) cleavage assay and DNA sequencing confirmed specific HBV gene cleavage and mutations at or around the gRNA target sites. Notably, this gene-editing system did not alter cellular viability or proliferation in the treated cells. Because of their rapid DNA cleavage capability, low off-target effects, low risk of insertional mutagenesis, and readiness for use in clinical application, these results suggest that synthetic gRNA/Cas9 RNP-based gene-editing can be utilized as a promising therapeutic drug for eradicating chronic HBV infection.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.